Structural, Biochemical, and Functional Characterization of the Calcium Sensor Neurocalcin δ in the Inner Retinal Neurons and Its Linkage with the Rod Outer Segment Membrane Guanylate Cyclase Transduction System

This study documents the detailed biochemical, structural, and functional identity of a novel Ca²⁺-modulated membrane guanylate cyclase transduction system in the inner retinal neurons. The guanylate cyclase is the previously characterized ROS-GC1 from the photoreceptor outer segments (PROS), and its new modulator is neurocalcin δ. At the membrane, the myristoylated form of neurocalcin δ senses submicromolar increments in free Ca²⁺, binds to its specific ROS-GC1 domain, and stimulates the cyclase. Neurocalcin δ is not present in PROS, indicating the absence of the pathway in the outer segments and the dissociation of its linkage with phototransduction. Thus, the pathway is linked specifically with the visual transduction machinery in the secondary neurons of the retina. With the inclusion of this pathway, the findings broaden the understanding of the existing mechanisms showing how ROS-GC1 is able to receive and transduce diverse Ca²⁺ signals into the cell-specific generation of second-messenger cyclic GMP in the retinal neurons.